EP3639025A1 - Procédé et appareil de criblage de donneur de sang à tube unique - Google Patents

Procédé et appareil de criblage de donneur de sang à tube unique

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Publication number
EP3639025A1
EP3639025A1 EP18730366.4A EP18730366A EP3639025A1 EP 3639025 A1 EP3639025 A1 EP 3639025A1 EP 18730366 A EP18730366 A EP 18730366A EP 3639025 A1 EP3639025 A1 EP 3639025A1
Authority
EP
European Patent Office
Prior art keywords
sample
testing
blood
serology
nat
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP18730366.4A
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German (de)
English (en)
Inventor
Michael Schmidt
Walid SIREIS
Erhard Seifried
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
DRK Blutspendedienst Baden Wuerttermberg Hessen gGmbH
Original Assignee
DRK Blutspendedienst Baden Wuerttermberg Hessen gGmbH
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Filing date
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Application filed by DRK Blutspendedienst Baden Wuerttermberg Hessen gGmbH filed Critical DRK Blutspendedienst Baden Wuerttermberg Hessen gGmbH
Publication of EP3639025A1 publication Critical patent/EP3639025A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/157—Devices characterised by integrated means for measuring characteristics of blood
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • B01D15/08—Selective adsorption, e.g. chromatography
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • B01D15/08—Selective adsorption, e.g. chromatography
    • B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
    • B01D15/38—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups B01D15/265 - B01D15/36
    • B01D15/3804—Affinity chromatography
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • B01D15/08—Selective adsorption, e.g. chromatography
    • B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
    • B01D15/38—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups B01D15/265 - B01D15/36
    • B01D15/3804—Affinity chromatography
    • B01D15/3809—Affinity chromatography of the antigen-antibody type, e.g. protein A, G, L chromatography
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • B01D15/08—Selective adsorption, e.g. chromatography
    • B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
    • B01D15/38—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups B01D15/265 - B01D15/36
    • B01D15/3804—Affinity chromatography
    • B01D15/3819—Affinity chromatography of the nucleic acid-nucleic acid binding protein type
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
    • G01N1/31—Apparatus therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/86—Signal analysis
    • G01N30/8651—Recording, data aquisition, archiving and storage
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5094—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for blood cell populations
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/52—Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5306—Improving reaction conditions, e.g. reduction of non-specific binding, promotion of specific binding
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/80—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood groups or blood types or red blood cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/10—Devices for withdrawing samples in the liquid or fluent state
    • G01N1/18—Devices for withdrawing samples in the liquid or fluent state with provision for splitting samples into portions
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N2021/0106—General arrangement of respective parts
    • G01N2021/0112—Apparatus in one mechanical, optical or electronic block
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06K—GRAPHICAL DATA READING; PRESENTATION OF DATA; RECORD CARRIERS; HANDLING RECORD CARRIERS
    • G06K1/00—Methods or arrangements for marking the record carrier in digital fashion

Definitions

  • the present invention relates to a method for the pre-analytical treatment of a blood sample to be analyzed, comprising a suitable sample matrix for said sample and suitably centrifuging said sample.
  • the present invention further relates to an apparatus, characterized in that it comprises suitable components for performing the method according to the present invention.
  • the present invention further relates to the use of said apparatus according to the present invention for the automated pre-analytical treatment of a blood sample to be analyzed according to the present invention.
  • Human blood is a highly valuable and hitherto indispensable raw material in medicine, which nowadays is used for extracting or manufacturing a large number of components and products.
  • NAT nucleic acid technologies
  • Blood donor screening can be divided into 3 parts (pre-analytic, analytic and post- analytic features).
  • the pre-analytic is important and crucial to achieve optimal analytic test results.
  • the analytical part can be subdivided into four groups (nucleic acid testing (NAT), serology testing, blood grouping and clinical chemistry).
  • NAT nucleic acid testing
  • serology testing serology testing
  • blood grouping blood grouping
  • clinical chemistry blood donor screening
  • the present invention solves this object by providing a method for the pre-analytical treatment of a blood sample to be analyzed, comprising the following steps: a) providing the sample to be analyzed in a suitable container, b) providing a suitable sample matrix for said sample, comprising an anticoagulant selected from KTiDTA, K 3 EDTA and sodium citrate in said container, c) centrifuging said sample of b) at about 2000 to 3400 x g for about 2 to 10 min, preferably for about 5 min at about 2600 x g; and d) subjecting said sample to analytical testing comprising at least two, at least three, preferably all, of i) serology testing, ii) clinical chemistry (CC) testing, iii) nucleic acid testing (NAT); and iv) blood typing.
  • steps b) to c) of the process can be performed repeatedly.
  • the present invention further solves the above object by providing an apparatus, characterized in that it comprises suitable components for performing the method according to the present invention.
  • the present invention further solves the above object by providing the use of said apparatus according to the present invention for the automated pre-analytical treatment of a blood sample to be analyzed according to the present invention.
  • STMS single tube management system
  • Said container comprises a compatible (or “harmonized") sample matrix (EDTA or citrate), and is subjected to compatible pre-analytical conditions (compatible time and speed of centrifugation).
  • the centrifugation time should be at about between 2 min and about 10 min with an optimal time of about 4 to 6 minutes, and the centrifugation should be between about 2,000 x g and about 4,000 x g with an optimal speed of about 2,400 x g to about 2,800 x g, with an optimum of about 2,600 x g.
  • the term "about” shall mean to include +/- 10% of the value as indicated.
  • Archiving can be done in suitable vials (preferably coded) using suitable buffers. The samples are usually stored in a freezer.
  • the sample must have a volume that is sufficient for performing the desired tests as described herein.
  • the sample has a volume of about 5 to 10 ml, and preferably of about 9 ml.
  • preferred volumes are selected from about 900 ul for serology, about 100 ul for CC, about 2 ml for NAT, and about 200 ul for blood typing (see also Figure 1).
  • any suitable vial can be used, which should be free of interfering chemicals (e.g. pyrogen-free), and stable under the desired conditions (e.g. temperature and centrifugation).
  • Preferred is the method according to the present invention, wherein said container is a sample tube, vial, or round bottom tube.
  • the sample matrix as provided to the sample(s) to be analyzed is either provided as a solution and/or a spray dried composition (see, for example, Leathern S et al. Equivalence of spray-dried K2EDTA, spray-dried K3EDTA, and liquid K3EDTA anticoagulated blood samples for routine blood center or transfusion service testing. Immunohematology. 2003; 19(4): 117-21), depending on the circumstances and the method(s) as used.
  • Preferred according to the present invention is a final, citrate concentration of about 0.005 to about 0.015 mmol/1, more preferred about 0.0109 mo 1/1 (0.32%) or about 0.0129 mo 1/1 (0.38%).
  • the amount of EDTA needed to avoid blood clotting can be readily adjusted by the person of skill, and is usually between about 1.5 and about 1.8 mg per 1 ml of blood. Potassium. EDTA.(K2 or K3) is more preferred, rather than Sodium EDTA, because Sodium. EDTA is less soluble in water.10% solution of potassium. EDTA. (w/v) in. distilled water is prepared as stock anticoagulant for hematological studies. To collect 1ml. blood, 10 ul of this solutio is added to the collectio tube.
  • the method according to the present invention is performed fully automated, without manual intervention.
  • the method according to the invention represents a single homogeneous process without manual intervention.
  • said blood sample to be analyzed is not a serum sample and/or does not comprise heparin.
  • inventive single tube management system (STMS) with compatible pre-analytical conditions is feasible for EDTA plasma samples as well as for citrate plasma samples, but it was found that it can not be used for serum samples (not feasible for blood grouping) and for heparin plasma samples (not feasible for NAT).
  • said blood sample to be analyzed is a pooled sample, e.g. of 2 to 15 samples.
  • the samples to be archived can be pooled samples. This is done in order to further streamline the process, where possible, or required. Pooling the blood samples is performed directly in containers labeled with barcodes or in the wells of plates.
  • the method of the present invention effectively eliminates the risk of mixing up samples, which existed with the previous method that involved partial manual steps for virus enrichment. For this purpose, the pooling of blood samples occurs directly in containers labeled with barcodes or in the wells of plates.
  • the method according to the present invention further comprises an additional centrifugation at about 2000 to 3400 x g for about 15 to 25 min, preferably for about 20 min at about 2600 x g, and a re-testing of serology according to the present invention, if the sample is initially reactive for said serology. That is, initially reactive samples for serology parameters could or should be re-tested in duplicate after an additional centrifugation of 20 min at 2,600 x g. This method further helps to avoid unspecific serology screening results.
  • Another aspect of the invention then relates to an apparatus, characterized in that it comprises suitable components for performing the method according to the present invention.
  • the apparatus according to the invention is suited for or suitable for generating the sample matrix, centrifugation, aliquot extraction, serology testing, clinical chemistry testing, nucleic acid extraction including, pooling, PCR preparation, blood typing, and/or raw data analysis.
  • the apparatus may comprise several components: - at least one automated pipetting workstation, - at least one barcode reader, - at least one fluid processing arm, and - at least one robotic arm, and if required and preferred - at least one amplification unit and - at least one detection unit.
  • the corresponding components are generally known to the person skilled in the art.
  • all components are designed as an integrated apparatus and are located within a housing unit.
  • the apparatus according to the invention is software- controlled.
  • the process can be controlled with software according to the invention.
  • the monitoring of the entire process can be achieved with software.
  • the software monitors the entire process.
  • the software provides worklists to the software programs of the individual sub-steps and processes, evaluates, and archives, e.g. error messages and sub-step results.
  • the software according to the invention can preferably be programmed to integrate centrifugation, extraction, PCR preparation and real-time PCR.
  • a further aspect of the invention comprises a computer program to control and monitor the method according to the invention.
  • Another aspect of the invention relates to the use of an apparatus according to the present invention for the, preferably automated, pre-analytical treatment of a blood sample to be analyzed according to the present invention.
  • the samples are preferably analyzed for the presence of nucleic acid, preferably for the presence of the nucleic acid of a virus such as HCV, HCMV, WNV, HIV, HBV, HAV, and PB 19.
  • a virus such as HCV, HCMV, WNV, HIV, HBV, HAV, and PB 19.
  • viruses may be selected from the group consisting of: human immunodeficiency virus 1 and 2 (HIV-1 and HIV-2), as well as HIV-1 subgroups M, N and O, hepatitis C virus (HCV), hepatitis B virus (HBV), cytomegalia virus (CMV, HHV 5), hepatitis A virus (HAV), hepatitis E virus, parvovirus B19 (PB 19), human T cell leukemia virus I/II (HTLV I/II), West Nile virus (WNV), SAPvS coronavirus (SARS CoV), MERS coronavirus, dengue and other viruses, as well as EBV, HHV 8, HGV/GBVC, TTV or Chikungunya.
  • HCV hepatitis C virus
  • HBV hepatitis B virus
  • CMV hepatitis A virus
  • HAV hepatitis E virus
  • PB 19 parvovirus B19
  • HTLV I/II human T cell le
  • the NAT detection method may comprise the amplification of nucleic acids, such as PCR, TaqMan PCR, Real Time-PCR, TMA, NASBA, SDA, or LCR.
  • a highly preferred embodiment of the method comprises nucleic acid amplification in the form of real-time PCR, which enables simultaneous online detection of the amplified nucleic acid.
  • a sample such as a blood donation sample
  • a barcode label to the final result and is identifiable by that barcode.
  • the automated, barcode-controlled nucleic acid extraction, amplification and detection following the concentration process rule out any mix-up of samples during the entire process.
  • the inventive method with compatible pre-analytical conditions is feasible for EDTA plasma samples as well as for citrate plasma samples, but it was found that it can not be used for serum samples (not feasible for blood grouping) and for heparin plasma samples (not feasible for NAT).
  • the challenge in the context of the invention was the harmonization of the pre-analytical conditions (in particular centrifugation time and centrifugation speed) for blood grouping and for serology testing.
  • centrifugation time should be between 2 min and 10 min with a preferred time of 5 min and with a centrifugation speed between 2,000 x g and 3,400 x g with a preferred speed of 2,600 x g.
  • the processed testing volume for four serological tests can be reduced to only 300 ⁇ 1. As shown in Figure 1 this enables to reduce the total number of sample tubes per donation to only one tube of 9 ml with the inventive single tube management system (STMS).
  • Central laboratories with approx. 6,000 blood donations per day thus can reduce the total number of sample tubes from approx. 18,000 sample tubes to 6,000 by using the method and single tube management system (STMS) of the invention.
  • STMS single tube management system
  • All sample tubes can be connected electronically at the donation side with the donation bags.
  • the staff has to check the filling volume of the single tube to avoid underfilled sample tubes. After an automated centrifugation a first barcoded aliquot tube will be pipetted by the pre-analytic instrument for serology testing.
  • a second aliquot sample tube will be prepared.
  • the original sample tube will preferably be used for NAT and blood grouping.
  • the STMS is an option to improve cost efficiency in automated track systems.
  • Figure 1 shows a schematic overview of a preferred embodiment of the single tube management system according to the invention.
  • the x-axis represents the centrifugation time (minutes, from 1 (left) to 20 (right) per column) and the y-axis the centrifugation in g (from 1000 (top) 4000 (bottom) in 200 x g increments).
  • Figure 2 A shows the analysis of NAT testing for HBV for diagnostic sensitivity.
  • Figure 2B shows the analysis of NAT testing for HBV for diagnostic specificity.
  • Figure 3 A shows the analysis of NAT testing for HCV for diagnostic sensitivity.
  • Figure 3B shows the analysis of NAT testing for HCV for diagnostic specificity.
  • Figure 4 A shows the analysis of NAT testing for HIV for diagnostic sensitivity.
  • Figure 4B shows the analysis of NAT testing for HIV for diagnostic specificity.
  • Figure 5A shows the analysis of serology testing for HBsAg for diagnostic sensitivity.
  • Figure 5B shows the analysis of serology testing for HBV for diagnostic specificity.
  • Figure 6A shows the analysis of serology testing for anti-HBc for diagnostic sensitivity.
  • Figure 6B shows the analysis of serology testing for anti-HBc for diagnostic specificity.
  • Figure 7 A shows the analysis of serology testing for anti-HCV for diagnostic sensitivity.
  • Figure 7B shows the analysis of serology testing for anti-HCV for diagnostic specificity.
  • Figure 8A shows the analysis of serology testing for HIV duo for diagnostic sensitivity.
  • Figure 8B shows the analysis of serology testing for HIV duo for diagnostic specificity.
  • Figure 9 shows the analysis of serology testing for blood grouping.
  • Figure 10 shows the analysis of clinical chemistry testing for IgG.
  • Figure 11 shows the analysis of clinical chemistry testing for total protein.
  • Figure 12A shows the analysis of NAT testing for HBV for diagnostic sensitivity.
  • Figure 12B shows the analysis of NAT testing for HBV for diagnostic specificity.
  • Figure 13A shows the analysis of NAT testing for HCV for diagnostic sensitivity.
  • Figure 13B shows the analysis of NAT testing for HCV for diagnostic specificity.
  • Figure 14A shows the analysis of NAT testing for HIV for diagnostic sensitivity.
  • Figure 14B shows the analysis of NAT testing for HIV for diagnostic specificity.
  • Figure 15 A shows the analysis of serology testing for HBsAg for diagnostic sensitivity.
  • Figure 15B shows the analysis of serology testing for HBV for diagnostic specificity.
  • Figure 16A shows the analysis of serology testing for anti-HBc for diagnostic sensitivity.
  • Figure 16B shows the analysis of serology testing for anti-HBc for diagnostic specificity.
  • Figure 17A shows the analysis of serology testing for anti-HCV for diagnostic sensitivity.
  • Figure 17B shows the analysis of serology testing for anti-HCV for diagnostic specificity.
  • Figure 18A shows the analysis of serology testing for HIV duo for diagnostic sensitivity.
  • Figure 18B shows the analysis of serology testing for HIV duo for diagnostic specificity.
  • Figure 19 shows the analysis of serology testing for blood grouping.
  • Figure 20 shows the analysis of clinical chemistry testing for IgG.
  • Figure 21 shows the analysis of clinical chemistry testing for total protein.
  • the object of the present invention is to achieve a compatibility (harmonization) of the sample tube matrix and the pre-analytical conditions (in particular centrifugation time and centrifugation speed) to enable all blood donor screening measurements from one sample tube without a substantial reduction of the diagnostic sensitivity and the diagnostic specificity.
  • Blood grouping tests All blood grouping tests were performed on the Beckman Coulter PK7300 instrument for the parameter A, B, 0, Rhesus and Kell. The following reagents were used in order to analyze the antigens and antibodies.
  • WHO standards for HBV (10/264), for HCV (06/102) and for HIV-1 (10/152) were diluted to final concentrations of 10 IU/ml, 50 IU/ml and 100 IU/ml, respectively.
  • the final virus concentration was spiked into whole blood samples.
  • Each concentration was tested for each pre-analytical condition (matrix belong on centrifugation time and centrifugation speed) in replicates of 10.
  • Data were analyzed by the number of positive NAT tests divided with the number of tested samples multiplied by 100. The studies on NAT were regarded as successful, if the diagnostic sensitivity was at least 90%.
  • Negative blood donor samples were tested for each pre-analytical condition (matrix belong on centrifugation time and centrifugation speed) in replicates of 100. Data were analyzed by the number of negative NAT tests divided with the number of tested samples multiplied by 100. The studies on NAT were regarded as successful if the diagnostic specificity was at least 95%.
  • Plasma from positive blood donors for HBsAg, anti-HBc, anti-HCV and anti-HIV-1 were diluted to final concentrations of 10 S/Co, 0.5 S/Co, 10 S/Co and 10 S/Co, respectively.
  • the anti-HBc test was performed as a competitive test, therefore positive samples have a S/Co value below 1.0.
  • the final virus concentration was spiked into whole blood samples. Each concentration was tested for each pre-analytical condition (matrix belong on centrifugation time and centrifugation speed) in replicates of 10. Data were analyzed by the number of positive NAT tests divided with the number of tested samples multiplied by 100. The studies on serology were regarded as successful, if the diagnostic sensitivity was at least 90%>.
  • Negative blood donor samples were tested for each pre-analytical condition (matrix belong on centrifugation time and centrifugations speed) in replicates of 100. Data were analyzed by the number of negative NAT tests divided with the number of tested samples multiplied by 100. The studies on serology are evaluated as successful if the diagnostic specificity is at least 95%.
  • the different centrifugation speeds were examined from 1 ,000 x g to 4,000 x g at intervals of 200 x g each.
  • Figure 2 A shows the analysis of NAT testing for HBV for diagnostic sensitivity.
  • the x- axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were evaluated as successful (pass) if at least 9/10 (90%) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 9/10 (90%) tests achieved a positive test result.
  • Figure 2B shows the analysis of NAT testing for HBV for diagnostic specificity.
  • the x- axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were evaluated as successful (pass) if at least 95/100 (95%) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 95/100 (95%>) tests achieved a positive test result.
  • Figure 3 A shows the analysis of NAT testing for HCV for diagnostic sensitivity.
  • the x- axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were evaluated as successful (pass) if at least 9/10 (90%>) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 9/10 (90%>) tests achieved a positive test result.
  • Figure 3B shows the analysis of NAT testing for HCV for diagnostic specificity.
  • the x- axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were evaluated as successful (pass) if at least 95/100 (95%>) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 95/100 (95%>) tests achieved a positive test result. Diagnostic sensitivity HIV
  • Figure 4A shows the analysis of NAT testing for HIV for diagnostic sensitivity.
  • the x- axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were evaluated as successful (pass) if at least 9/10 (90%) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 9/10 (90%) tests achieved a positive test result.
  • Figure 4B shows the analysis of NAT testing for HIV for diagnostic specificity.
  • the x- axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were evaluated as successful (pass) if at least 95/100 (95%) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 95/100 (95%>) tests achieved a positive test result.
  • Figure 5A shows the analysis of serology testing for HBsAg for diagnostic sensitivity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were evaluated as successful (pass) if at least 9/10 (90%)) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 9/10 (90%>) tests achieved a positive test result.
  • Figure 5B shows the analysis of serology testing for HBV for diagnostic specificity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were evaluated as successful (pass) if at least 95/100 (95%o) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 95/100 (95%>) tests achieved a positive test result.
  • Figure 6A shows the analysis of serology testing for anti-HBc for diagnostic sensitivity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were evaluated as successful (pass) if at least 9/10 (90%) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 9/10 (90%>) tests achieved a positive test result.
  • Figure 6B shows the analysis of serology testing for anti-HBc for diagnostic specificity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were evaluated as successful (pass) if at least 95/100 (95%) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 95/100 (95%>) tests achieved a positive test result.
  • Figure 7 A shows the analysis of serology testing for anti-HCV for diagnostic sensitivity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were evaluated as successful (pass) if at least 9/10 (90%>) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 9/10 (90%>) tests achieved a positive test result.
  • Figure 7B shows the analysis of serology testing for anti-HCV for diagnostic specificity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were evaluated as successful (pass) if at least 95/100 (95%>) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 95/100 (95%>) tests achieved a positive test result.
  • Figure 8A shows the analysis of serology testing for HIV duo for diagnostic sensitivity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if at least 9/10 (90%)) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 9/10 (90%>) tests achieved a positive test result. Diagnostic specificity HIV duo
  • Figure 8B shows the analysis of serology testing for HIV duo for diagnostic specificity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if at least 95/100 (95%) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 95/100 (95%) tests achieved a positive test result.
  • Figure 9 shows the analysis of serology testing for blood grouping.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if data were comparable to the blood typing data under the current routine conditions.
  • Figure 10 shows the analysis of clinical chemistry testing for IgG.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre- analytical conditions were regarded as successful (pass) if data were comparable to the clinical chemistry data under the current routine conditions.
  • Figure 11 shows the analysis of clinical chemistry testing for total protein.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if data were comparable to the clinical chemistry data under the current routine conditions.
  • Figure 12A shows the analysis of NAT testing for HBV for diagnostic sensitivity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if at least 9/10 (90%) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 9/10 (90%) tests achieved a positive test result.
  • Figure 12B shows the analysis of NAT testing for HBV for diagnostic specificity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if at least 95/100 (95%) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 95/100 (95%>) tests achieved a positive test result.
  • Figure 13A shows the analysis of NAT testing for HCV for diagnostic sensitivity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if at least 9/10 (90%)) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 9/10 (90%>) tests achieved a positive test result.
  • Figure 13B shows the analysis of NAT testing for HCV for diagnostic specificity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if at least 95/100 (95%o) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 95/100 (95%>) tests achieved a positive test result.
  • Figure 14A shows the analysis of NAT testing for HIV for diagnostic sensitivity.
  • the x- axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if at least 9/10 (90%>) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 9/10 (90%>) tests achieved a positive test result.
  • Diagnostic specificity HIV Figure 14B shows the analysis of NAT testing for HIV for diagnostic specificity.
  • the x- axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if at least 95/100 (95%) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 95/100 (95%>) tests achieved a positive test result.
  • Figure 15 A shows the analysis of serology testing for HBsAg for diagnostic sensitivity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if at least 9/10 (90%)) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 9/10 (90%>) tests achieved a positive test result.
  • Figure 15B shows the analysis of serology testing for HBV for diagnostic specificity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if at least 95/100 (95%o) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 95/100 (95%>) tests achieved a positive test result.
  • Figure 16A shows the analysis of serology testing for anti-HBc for diagnostic sensitivity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if at least 9/10 (90%>) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 9/10 (90%>) tests achieved a positive test result.
  • Figure 16B shows the analysis of serology testing for anti-HBc for diagnostic specificity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if at least 95/100 (95%) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 95/100 (95%>) tests achieved a positive test result.
  • Figure 17A shows the analysis of serology testing for anti-HCV for diagnostic sensitivity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if at least 9/10 (90%>) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 9/10 (90%>) tests achieved a positive test result.
  • Figure 17B shows the analysis of serology testing for anti-HCV for diagnostic specificity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if at least 95/100 (95%>) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 95/100 (95%>) tests achieved a positive test result.
  • Figure 18A shows the analysis of serology testing for HIV duo for diagnostic sensitivity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if at least 9/10 (90%>) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 9/10 (90%>) tests achieved a positive test result.
  • Figure 18B shows the analysis of serology testing for HIV duo for diagnostic specificity.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if at least 95/100 (95%>) tests achieved a positive test result.
  • the pre-analytical conditions were regarded as not successful if less than 95/100 (95%) tests achieved a positive test result.
  • Figure 19 shows the analysis of serology testing for blood grouping.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if data were comparable to the blood typing data under the current routine conditions.
  • Figure 20 shows the analysis of clinical chemistry testing for IgG.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre- analytical conditions were regarded as successful (pass) if data were comparable to the clinical chemistry data under the current routine conditions.
  • Figure 21 shows the analysis of clinical chemistry testing for total protein.
  • the x-axis represents the centrifugation time (minutes) and the y-axis the centrifugation speed.
  • the pre-analytical conditions were regarded as successful (pass) if data were comparable to the clinical chemistry data under the current routine conditions.

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Abstract

La présente invention concerne un procédé de traitement pré-analytique d'un échantillon de sang à analyser, comprenant une matrice d'échantillon appropriée pour ledit échantillon et la centrifugation appropriée dudit échantillon. La présente invention concerne en outre un appareil, caractérisé en ce qu'il comprend des composants appropriés pour mettre en oeuvre le procédé selon la présente invention. La présente invention concerne en outre l'utilisation dudit appareil selon la présente invention pour le traitement pré-analytique automatisé d'un échantillon de sang à analyser selon la présente invention.
EP18730366.4A 2017-06-16 2018-06-15 Procédé et appareil de criblage de donneur de sang à tube unique Withdrawn EP3639025A1 (fr)

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